The effect of three different 1.2 MAC combinations of nitrous oxide (N2O) and enflurane upon glucose metabolism in the central nervous system was evaluated in male rats (n = 30). Anesthesia was induced with enflurane and N2O prior to tracheal intubation and mechanical ventilation. Physiologic variables (temperature, blood pressure, pH, PaO2, PaCO2, serum glucose, and hematocrit) were maintained within normal limits. Each rat was randomly assigned one of the following 1.2 MAC anesthetic regimens: 1) control--0% N2O/2.76% enflurane, 2) treatment 1--30% N2O/2.26% enflurane, or 3) treatment II--60% N2O/2.12% enflurane. Following anesthetic equilibration, an autoradiographic evaluation of local cerebral and spinal cord glucose utilization was performed. There were no differences in the physiologic data. As enflurane was partially replaced by an equivalent MAC fraction of N2O (0-30%), a heterogeneous activation of cerebral metabolism was observed in selected sensory input structures, and in components of the limbic system. The values tended to return to control when N2O was increased to 60% (and the enflurane was appropriately reduced). At all spinal cord levels, a homogeneous increase in metabolism was observed in both white and grey matter when enflurane was replaced by the 0-30% N2O change, with a return to control when the N2O was further increased from 30-60%. Thus, in rats, increasing the N2O concentration (while concurrently decreasing enflurane) produced a biphasic metabolic response. Metabolism was activated when N2O was increased from 0-30%, with a relative depression in metabolism when N2O was further increased from 30-60%.(ABSTRACT TRUNCATED AT 250 WORDS)